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rdf:type |
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lifeskim:mentions |
umls-concept:C0002844,
umls-concept:C0007634,
umls-concept:C0205263,
umls-concept:C1280500,
umls-concept:C1332397,
umls-concept:C1514873,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636,
umls-concept:C1709061,
umls-concept:C1879547
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pubmed:issue |
4
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pubmed:dateCreated |
2011-2-28
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pubmed:abstractText |
The present report investigated the pathway(s) involved in the inhibition of apoptosis by the synthetic androgen, R1881 in serum-starved LNCaP cells exposed to the pi3K inhibitor, LY294002. R1881 blocked LY294002-induced apoptosis through the inhibition of Bak activation via an increase in Bcl-xL transcription and protein expression. In addition, R1881 treatment enhanced the stability of the Pim-1 kinase, resulting in the inhibition of the activation of the BH3-only protein Bad through its phosphorylation at ser75. Pharmacological inhibition of the Pim-1 kinase activity with quercetagetin, a highly selective Pim-1 inhibitor, prevented R1881-mediated increase in Bad phosphorylation and restored cell sensitivity to LY294002-induced apoptosis despite the increase in Bcl-xL expression. These results demonstrate for the first time that the inhibition of LY294002-induced apoptosis by androgen is a function of an androgen receptor-dependent genomic signaling pathway leading to an increase in Bcl-xL expression as well as a non-genomic, Pim-1-dependent, signaling pathway mediated via phosphorylation of Bad at ser75.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-(4-morpholinyl)-8-phenyl-4H-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/Androgens,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Serum-Free,
http://linkedlifedata.com/resource/pubmed/chemical/Metribolone,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-pim-1,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2 Homologous Antagonist-Killer...,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-Associated Death Protein,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1878-5875
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pubmed:author |
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
43
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
594-603
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pubmed:meshHeading |
pubmed-meshheading:21187157-Androgens,
pubmed-meshheading:21187157-Cell Line, Tumor,
pubmed-meshheading:21187157-Cell Survival,
pubmed-meshheading:21187157-Chromones,
pubmed-meshheading:21187157-Culture Media, Serum-Free,
pubmed-meshheading:21187157-Enzyme Activation,
pubmed-meshheading:21187157-Enzyme Stability,
pubmed-meshheading:21187157-Gene Expression Regulation,
pubmed-meshheading:21187157-Half-Life,
pubmed-meshheading:21187157-Humans,
pubmed-meshheading:21187157-Metribolone,
pubmed-meshheading:21187157-Morpholines,
pubmed-meshheading:21187157-Phosphorylation,
pubmed-meshheading:21187157-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:21187157-Proto-Oncogene Proteins c-pim-1,
pubmed-meshheading:21187157-Serine,
pubmed-meshheading:21187157-Signal Transduction,
pubmed-meshheading:21187157-bcl-2 Homologous Antagonist-Killer Protein,
pubmed-meshheading:21187157-bcl-Associated Death Protein,
pubmed-meshheading:21187157-bcl-X Protein
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pubmed:year |
2011
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pubmed:articleTitle |
Activation of a non-genomic Pim-1/Bad-Pser75 module is required for an efficient pro-survival effect of Bcl-xL induced by androgen in LNCaP cells.
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pubmed:affiliation |
Department of Biochemistry, Yong Loo Lin School of Medicine, NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 119260, Singapore.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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